PROJECT SUMMARY Candidate: Dr. Nathan Brummel, MD, MSCI is an Instructor in Medicine at the Vanderbilt University Medical Center (VUMC) with a strong background in aging and critical care research through his prior studies of long- term outcomes in survivors of critical illness and formal training in clinical research. His immediate career goal is to gain the skills necessary to lead an independent, productive program of interdisciplinary aging critical care research. His long-term career plan is to become a physician-scientist recognized as the national (and eventually international) leader in advancing the understanding of disabling processes following critical illness through publications involving better tools by which to understand mechanisms and then design and conduct randomized controlled trials of novel interventional strategies to improve patients' clinical outcomes. Research Project: Nearly two-thirds of all patients hospitalized for a critical illness are age 65 years or older. While these patients are more likely than ever to survive their illness, up to 75% will suffer with newly acquired or worsened disabilities. Thus, there is a looming and under-addressed public health problem that is emerging in the form of large and growing numbers of survivors of a critical illness with life-altering disabilities. A better understanding of the underlying risk factors for disability following critical illness is greatly needed. The Specific Aims of the proposed research are: a) To test the hypothesis that greater activity during critical illness will be independently associated with a lower prevalence, less severity and shorter duration of disability in activities of daily living and mobility at 3- and 12-month follow-up, b) To test the hypothesis that greater activity during critical illness will be independently associated with better physical function and cognitive function at 3- and 12- month follow-up, and c) To test the hypothesis that greater physical activity during critical illness will reduce biomarkers of systemic inflammation and coagulation at hospital discharge. Career Development: Dr. Brummel's career development plan integrates formal coursework with personalized training with his mentors and collaborators to: a) develop a strong scientific foundation in the disability process, physical and cognitive impairments after critical illness, the measurement of activity during critical illness, and the biological mechanisms of disability after critical illness; b) bolster his skills in clinical trials and biostatistics; c) strengthen his already robust leadership skills; and d) augment his training in geriatrics and gerontology. Environment: VUMC is the ideal environment to allow Dr. Brummel to become a nationally recognized leader in aging and critical care-related translational research of the disabling process following critical illness. The environment includes a strong team of NIH-funded mentors and collaborators, an internationally known ICU Delirium and Cognitive Impairment Study Group, and dynamic support from the Vanderbilt Institute for Clinical and Translational Research. Using data obtained in the proposed study, Dr. Brummel will develop and test future interventions to reduce disability after critical illness that will ultimately impact ICU care worldwide.